Role of ctDNA change as a response measure in the EA1183 patient population and how ctDNA changes correlate with metabolic response by serial FDG PET/CT

ctDNA 变化作为 EA1183 患者群体反应指标的作用以及 ctDNA 变化如何与连续 FDG PET/CT 的代谢反应相关

• 批准号: 10449101
• 负责人: Jennifer Marie Specht
• 金额: $ 37.39万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-15 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10449101
• 关键词: American College of Radiology Imaging Network; Biological Assay; Biological Markers; Blood; Categories; Clinic; Clinical; Clinical Trials; Collection; Data Set; Disease; Disease Progression; Eastern Cooperative Oncology Group; Enrollment; Future; Generations; Genomics; Goals; Guidelines; Image; Lesion; Liquid substance; Malignant Bone Neoplasm; Measurable Disease; Measurement; Measures; Metabolic; Metastatic Neoplasm to the Bone; Metastatic breast cancer; Methods; Modality; Monitor; Multi-Institutional Clinical Trial; Outcome; Outcome Study; PET/CT scan; Patients; Progression-Free Survivals; Residual Tumors; Resistance; Role; Scanning; Site; Systemic Therapy; Testing; Time; Tracer; Tumor Biology; Tumor Markers; X-Ray Computed Tomography; base; blood-based biomarker; bone; burden of illness; cancer therapy; circulating biomarkers; clinical practice; clinical predictors; design; experience; fluorodeoxyglucose positron emission tomography; genome sequencing; glucose metabolism; imaging approach; imaging biomarker; improved; liquid biopsy; malignant breast neoplasm; patient population; patient response; predicting response; prospective; response; skeletal-related events; tool; treatment response; tumor; tumor DNA; tumor metabolism; uptake; whole genome; American College of Radiology Imaging Network; Biological Assay; Biological Markers; Blood; Categories; Clinic; Clinical; Clinical Trials; Collection; Data Set; Disease; Disease Progression; Eastern Cooperative Oncology Group; Enrollment; Future; Generations; Genomics; Goals; Guidelines; Image; Lesion; Liquid substance; Malignant Bone Neoplasm; Measurable Disease; Measurement; Measures; Metabolic; Metastatic Neoplasm to the Bone; Metastatic breast cancer; Methods; Modality; Monitor; Multi-Institutional Clinical Trial; Outcome; Outcome Study; PET/CT scan; Patients; Progression-Free Survivals; Residual Tumors; Resistance; Role; Scanning; Site; Systemic Therapy; Testing; Time; Tracer; Tumor Biology; Tumor Markers; X-Ray Computed Tomography; base; blood-based biomarker; bone; burden of illness; cancer therapy; circulating biomarkers; clinical practice; clinical predictors; design; experience; fluorodeoxyglucose positron emission tomography; genome sequencing; glucose metabolism; imaging approach; imaging biomarker; improved; liquid biopsy; malignant breast neoplasm; patient population; patient response; predicting response; prospective; response; skeletal-related events; tool; treatment response; tumor; tumor DNA; tumor metabolism; uptake; whole genome

Project Summary: Patients with bone dominant (BD) and bone only (BO) metastatic breast cancer (MBC) represent a large patient population1,2 who are often excluded from clinical trials using RECIST 1.1 as the primary response assessment because bone lesions are classified as non-measurable, non-target lesions3. Current blood-based biomarkers such as tumor markers (CA15.3, CA27.29 and CEA) have similarly shown limited utility in assessing response to therapy in patients with MBC. There is therefore an important need for better measures of therapeutic response for patients with BD MBC. EA1183 FEATURE is a prospective, multicenter clinical trial approved by the NCI and sponsored by ECOG-ACRIN designed to evaluate the value of serial FDG-PET/CT to assess response in BD MBC. The trial will test the ability of tumor metabolic changes to predict the clinically meaningful outcomes of progression free survival (PFS) and time to skeletal-related event (tSRE). Measurement and characterization of ctDNA provides an option of non-invasively evaluating both disease burden and emergence of genomic changes in tumor biology. We propose to integrate fluid-based tumor monitoring (by serial collection of circulating tumor DNA, ctDNA) and FDG-PET/CT imaging to determine if these biomarkers, separately or combined, can predict a response to therapy for in patients with BO or BD MBC participating in the EA1183 FEATURE trial. We will also assess the extent to which FDG-PET/CT, ctDNA, or both can predict PFS as early as 4 weeks into therapy. We hypothesize that integration of imaging (FDG-PET/CT) and fluid-based, liquid biopsy (ctDNA) assays may permit characterization of therapy response for patients with BO and BD MBC in advance of currently used methods, possibly as early as 4 weeks. This R01 proposal will provide support for additional objectives in EA1183, which are the aims of our proposal: 1.) to assess ability of qualitative and quantitative changes in serial ctDNA measures to predict PFS and time to SRE in patients with BO or BD MBC beginning new systemic therapy in EA1183; 2) to determine if early metabolic changes in bone metastases assessed by FDG-PET/CT at 4 weeks after start of systemic therapy predict PFS and tSRE in patients with BO or BD MBC; 3) to evaluate the relationship between changes in ctDNA and metabolic response as assessed by FDG-PET/CT and to test the combined ability of FDG-PET/CT and ctDNA at 4 and 12 weeks after the start of new systemic therapy to predict PFS and SRE. The outcome of this study will be the generation of robust response endpoints for BD MBC to provide access to clinical trials and guide clinic al practice for the large group of patients with this type of MBC.

项目摘要： 骨头显性骨骼（BD）和骨（BO）转移性乳腺癌（MBC）的患者代表大型 患者人群1,2通常被排除在临床试验之外，使用recist 1.1作为主要反应 评估是因为骨骼病变被归类为不可衡量的非目标病变3。目前的血液 诸如肿瘤标记物（CA15.3，CA27.29和CEA）之类的生物标志物也显示出有限的效用 评估MBC患者对治疗的反应。因此，重要的是要采取更好的措施 BD MBC患者的治疗反应。 EA1183功能是一项预期的多中心临床试验 由NCI批准并由Ecog-Acrin赞助，旨在评估串行FDG-PET/CT的价值 评估BD MBC中的响应。该试验将测试肿瘤代谢变化以预测临床上的能力 有意义的自由生存（PFS）和与骨骼相关事件的时间（TSRE）的有意义的结果。 CTDNA的测量和表征提供了一种非侵入性评估这两种疾病的选择 肿瘤生物学基因组变化的负担和出现。我们建议整合基于流体的肿瘤 监测（通过循环肿瘤DNA，CTDNA的序列收集）和FDG-PET/CT成像 这些分别或组合的生物标志物可以预测BO或BD患者对治疗的反应 MBC参加了EA1183功能试验。我们还将评估FDG-PET/CT的程度， CTDNA或两者都可以在治疗后4周内预测PF。我们假设成像的整合 （FDG-PET/CT）和基于流体的液体活检（CTDNA）测定法可能允许表征治疗反应 对于BO和BD MBC的患者，可能早在4周之前就使用了当前使用的方法。这 R01提案将为EA1183中的其他目标提供支持，这是我们建议的目的：1。） 评估串行CTDNA测量中定性和定量变化的能力，以预测PFS和时间的时间 在BO或BD MBC的患者中，EA1183开始了新的全身疗法； 2）确定早期代谢是否 全身治疗开始后4周，由FDG-PET/CT评估的骨转移的变化预测PFS 和BO或BD MBC患者的TSRE； 3）评估ctDNA和 由FDG-PET/CT评估的代谢反应，并测试FDG-PET/CT和CTDNA的组合能力 在新的系统疗法开始后的4和12周，以预测PFS和SRE。这项研究的结果 将是BD MBC的强大响应终点，以提供临床试验的访问和指南 这类MBC的大量患者的诊所实践。